Heart Failure, DiastolicPhase 4EMMED-HFNCT04071626
Evaluating Metabolic Mechanisms of Ertugliflozin in Diabetes & Heart Failure
A Phase 4 study testing Ertugliflozin 5 mg in people with Heart Failure, Diastolic and Diabetes Mellitus, Type 2, run by University Hospitals Cleveland Medical Center at 1 site in United States.
Trial summary
This clinical trial will determine if subjects with heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus (DM2) receiving sodium-glucose cotransporter 2 (SGLTi2) inhibitor therapy (ertugliflozin) alters cardiac metabolism compared to placebo in a single blinded (to subject), randomized… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Heart Failure, Diastolic, Diabetes Mellitus, Type 2
- What is being tested?
- Ertugliflozin 5 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2020to 11 Jan 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years old but < 75 years old
- No HF hospitalization within 6 months
- Overweight or Obesity defined as BMI > 29 but < 42
- History of insulin resistance or T2DM and on oral diabetes agents other than SGLT2i (HgbA1c > 5.8% and < 10.5%)
- EF calculated based on a recent echo/cath/nuclear study at screening (pre-enrollment) > 50%
- Stable HFpEF (HF with preserved ejection fraction) medications use of 3 months with no plans to changes or add medications for at least 12 weeks course of the study)
Who cannot join
- Acute HFpEF hospitalization within 6 months of enrollment.
- CKD stage 4 or 5 (eGFR < 30 ml/min by CKD-EPI equation).
- Other known causes of HF including poorly controlled hypertension (SBP >160 mm Hg) or ischemic cardiomyopathy (etc).
- Anemia (Hgb < 11.0 mg/dL for women and < 12.0 mg/dL for men) or severe thrombocytopenia (platelets < 50,000 mm3)
- Anticipated changing of HF medication during anticipated study period.
- HFREF (LV EF < 50%).
- Acute coronary syndrome, transient ischemic attack, CVA or critical limb ischemia during the last 6 months or coronary/peripheral revascularization within the last 3 months. Severe life threatening illness or live expectancy < 6 months.
- Contraindications to MRI (metallic implants, severe claustrophobia) or treadmill exercise (limb amputation, severe osteoarthritis or equivalent functional mechanical limitation).
Trial locations and contacts
1 site in 1 country.
United States1 site
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
About this study
Official title: The EMMED-HF Study: Evaluating Metabolic Mechanisms of Ertugliflozin in Diabetes & Heart Failure
This clinical trial will determine if subjects with heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus (DM2) receiving sodium-glucose cotransporter 2 (SGLTi2) inhibitor therapy (ertugliflozin) alters cardiac metabolism compared to placebo in a single blinded (to subject), randomized, parallel group, active controlled, single center experimental design.
Read the detailed description
The results of recent sodium-glucose cotransporter 2 (SGLT2) inhibitor therapy clinical trials demonstrate clinically significant reductions in cardiovascular endpoints (myocardial infarction, cardiac death, heart failure hospitalization). SGLT2 inhibition appears to exert cardiovascular protection through pleiotrophic effects involving both the myocardium and peripheral organs but the primary pathway of risk reduction of heart failure incidents has not been elucidated. SGLT2 inhibitors induce a loss of 50-100 grams of glucose through urinary excretion daily. There is a compensatory increase in ketone body production in the liver after initiation of SGLT inhibition. Ketone bodies are the most energy efficient myocardial fuel source and reduce myocardial oxidative stress when consumed as the primary energy substrate. Inducing a shift to ketone body metabolism to improves cardiac diastolic performance suggests a unifying paradigm of direct myocardial effect and peripheral metabolic flexibility through which SGLT2 inhibition mediates myocardial protection in HFpEF.
Specific Aims Aim 1: Determine if 12 weeks of SGLTi2 therapy improves peak exercise oxygen uptake compared to placebo. We will perform cardiac MRI exercise testing (CPET-ExMR) before and \& post 12 weeks of therapy to measure cardiopulmonary fitness by metabolic cart gas exchange and left ventricular myocardial mass.
Aim 2: Evaluate the short term (12 weeks effect of SGLTi on metabolic flexibility in HFpEF compared to baseline function and control group. We will measure glucose and lipid metabolism response to SGLT2 inhibition. Serum samples of glucose and ketone bodies (β-hydroxybutyrate) will be assessed before \& post 12 weeks of therapy. Serial serum samples will allow us to generate metabolomics profiles before and after treatment. This experimental design will provide insight into ketone body production, peripheral glucose flux, and circulating lipoparticles in response to SGLTi therapy.
- Being tested
- Ertugliflozin 5 mg, Placebo oral tablet
- Keywords
- ertugliflozin, SGLT2 inhibtion, Cardiovascular Diseases, Sodium-Glucose Transporter 2 Inhibitors, Glucose Metabolism Disorders, Physiological Effects of Drugs, Diabetes Mellitus, Diabetes Mellitus, Type 2, Endocrine System Diseases
- Medical subject headings
- Heart Failure, Diastolic, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Glucose Metabolism Disorders, Diabetes Mellitus, Endocrine System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ertugliflozin 5 mgDrug
Ertugliflozin 5 mg once a day for 12 weeks
Placebo oral tabletDrug
Placebo oral tablet once a day for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Ertugliflozin Treatment Arm | Experimental | Ertugliflozin 5 mg tablet once a day for 12 weeks Receives: Drug: Ertugliflozin 5 mg |
| Placebo | Placebo comparator | Placebo tablet once a day for 12 weeks Receives: Drug: Placebo oral tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak VO2, ml/kg/Min, as Measured by Metabolic Gas Exchange
The difference in peak oxygen uptake as measured by peak VO2 (ml/kg/min) between ertugliflozin and placebo as measured at baseline and after 12 weeks of treatment
Measured: 12 weeks
Secondary outcomes (2)
Left Ventricular Mass Index (gm/m2), as Measured by Cardiac MRI
The difference in LV mass index (gm/m2) measured by cardiac MRI between ertugliflozin and placebo as measured at baseline and after 12 weeks of treatment
Measured: 12 weeks
Serum Ketone Bodies (Betahydroxybutyrate)
The difference in serum ketone bodies (betahydroxybutyrate) levels between ertugliflozin and placebo as measured at baseline and after 12 weeks of treatment
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2019
- Study start1 Mar 2020
- Primary completion11 Jan 2023
- Study completion11 Jan 2023
Why it stopped: Lack of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Heart Failure, DiastolicStudies of the same condition, open and under way.
- More trials run by University Hospitals Cleveland Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel assignment, active controlled, single center experimental design.
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospitals Cleveland Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Trevor Jenkins, University Hospitals Cleveland Medical Center
- Investigators
- Trevor L Jenkins, MD, Principal investigator, University Hospitals Cleveland Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04071626
- Sponsor's protocol ID
- STUDY20190016
- Acronym
- EMMED-HF
- Status last verified
- Dec 2023
- First submitted
- 26 Aug 2019
- Last updated
- 13 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The EMMED-HF Study: Evaluating Metabolic Mechanisms of Ertugliflozin in Diabetes & Heart Failure
- ClinicalTrials.gov ID
- NCT04071626
- Acronym / sponsor ID
- EMMED-HF / STUDY20190016
- Keywords
- ertugliflozin, SGLT2 inhibtion, Cardiovascular Diseases, Sodium-Glucose Transporter 2 Inhibitors, Glucose Metabolism Disorders, Physiological Effects of Drugs, Diabetes Mellitus, Diabetes Mellitus, Type 2
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of enrollment
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University Hospitals Cleveland Medical CenterUniversity, hospital or other
- Study start
- 1 Mar 2020 (actual)
- Primary completion
- 11 Jan 2023 (actual)
- Study completion
- 11 Jan 2023 (actual)
- First posted
- 28 Aug 2019 (actual)
- Results
- Posted 13 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical trial will determine if subjects with heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus (DM2) receiving sodium-glucose cotransporter 2 (SGLTi2) inhibitor therapy (ertugliflozin) alters cardiac metabolism compared to placebo in a single blinded (to subject), randomized, parallel group, active controlled, single center experimental design.
Detailed description
The results of recent sodium-glucose cotransporter 2 (SGLT2) inhibitor therapy clinical trials demonstrate clinically significant reductions in cardiovascular endpoints (myocardial infarction, cardiac death, heart failure hospitalization). SGLT2 inhibition appears to exert cardiovascular protection through pleiotrophic effects involving both the myocardium and peripheral organs but the primary pathway of risk reduction of heart failure incidents has not been elucidated. SGLT2 inhibitors induce a loss of 50-100 grams of glucose through urinary excretion daily. There is a compensatory increase in ketone body production in the liver after initiation of SGLT inhibition. Ketone bodies are the most energy efficient myocardial fuel source and reduce myocardial oxidative stress when consumed as the primary energy substrate. Inducing a shift to ketone body metabolism to improves cardiac diastolic performance suggests a unifying paradigm of direct myocardial effect and peripheral metabolic flexibility through which SGLT2 inhibition mediates myocardial protection in HFpEF.
Specific Aims Aim 1: Determine if 12 weeks of SGLTi2 therapy improves peak exercise oxygen uptake compared to placebo. We will perform cardiac MRI exercise testing (CPET-ExMR) before and \& post 12 weeks of therapy to measure cardiopulmonary fitness by metabolic cart gas exchange and left ventricular myocardial mass.
Aim 2: Evaluate the short term (12 weeks effect of SGLTi on metabolic flexibility in HFpEF compared to baseline function and control group. We will measure glucose and lipid metabolism response to SGLT2 inhibition. Serum samples of glucose and ketone bodies (β-hydroxybutyrate) will be assessed before \& post 12 weeks of therapy. Serial serum samples will allow us to generate metabolomics profiles before and after treatment. This experimental design will provide insight into ketone body production, peripheral glucose flux, and circulating lipoparticles in response to SGLTi therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
- Model description
- Parallel assignment, active controlled, single center experimental design.
| Arm | Type | Receives |
|---|---|---|
| Ertugliflozin Treatment Arm | Experimental | Drug: Ertugliflozin 5 mgErtugliflozin 5 mg tablet once a day for 12 weeks |
| Placebo | Placebo comparator | Drug: Placebo oral tabletPlacebo tablet once a day for 12 weeks |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age > 18 years old but < 75 years old
- No HF hospitalization within 6 months
- Overweight or Obesity defined as BMI > 29 but < 42
- History of insulin resistance or T2DM and on oral diabetes agents other than SGLT2i (HgbA1c > 5.8% and < 10.5%)
- EF calculated based on a recent echo/cath/nuclear study at screening (pre-enrollment) > 50%
Key exclusion criteria (8 listed)
- Acute HFpEF hospitalization within 6 months of enrollment.
- CKD stage 4 or 5 (eGFR < 30 ml/min by CKD-EPI equation).
- Other known causes of HF including poorly controlled hypertension (SBP >160 mm Hg) or ischemic cardiomyopathy (etc).
- Anemia (Hgb < 11.0 mg/dL for women and < 12.0 mg/dL for men) or severe thrombocytopenia (platelets < 50,000 mm3)
- Anticipated changing of HF medication during anticipated study period.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ertugliflozin 5 mgErtugliflozin 5 mg once a day for 12 weeks | Drug | Ertugliflozin Treatment Arm |
| Placebo oral tabletPlacebo oral tablet once a day for 12 weeks | Drug | Placebo |
Primary outcome
Peak VO2, ml/kg/Min, as Measured by Metabolic Gas Exchange
Time frame: 12 weeks
The difference in peak oxygen uptake as measured by peak VO2 (ml/kg/min) between ertugliflozin and placebo as measured at baseline and after 12 weeks of treatment
2 secondary outcomes
Left Ventricular Mass Index (gm/m2), as Measured by Cardiac MRI
Time frame: 12 weeks
Serum Ketone Bodies (Betahydroxybutyrate)
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Trevor L Jenkins, MD principal investigator
University Hospitals Cleveland Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ertugliflozin 5 mg in people with Heart Failure, Diastolic and Diabetes Mellitus, Type 2, run by University Hospitals Cleveland Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak VO2, ml/kg/Min, as Measured by Metabolic Gas Exchange (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2023.